细胞周期蛋白与肺癌

细胞周期蛋白是细胞周期调控的核心因子，其中，细胞周期蛋白Ｄ１已被公认为一个新的致癌基因。在人类多种肿瘤中常常出现细胞周期蛋白的异常表达，并与肿瘤的发生、发展密切相关。本文就近年来关于细胞周期蛋白的致癌机制及其在肺癌研究中的进展作一综述。     

细胞周期蛋白与消化道肿瘤

近来细胞周期蛋白 (cyclin)在细胞恶性转化过程中的作用越来越受到重视。Cyclin是在从酵母到人类等真核生物中有广泛作用的分子 ,它与细胞周期蛋白依赖性激酶 (cyclin dependentkinase ,CDK)、细胞周期蛋白依赖性激酶抑制因子 (cyclin dependentkinaseinhibitor,CKI)一起参与细胞周期调控。近年的研究显示 ,肿瘤的发生、发展和恶变与细胞周期调控的失调密切相关 ,因而cyclin与肿瘤的关系已引起众多学者的兴趣。本文就cyclin在消化道肿瘤中的研究作一综述。—、细胞周期蛋白 (cyclin)与细胞周期在哺乳动物中细胞周期是由激活的各种蛋白复…     

YB-1与肝纤维化及肝癌关系的研究进展

Y-box结合蛋白-1（YB-1）在肝纤维化中起着重要的抑制作用。细胞因子Hsc025可与YB-1蛋白C端的氨基酸序列结合，引导后者的核转位，从而阻断TGF-β／Smad信号转导而抑制胶原基因表达；干扰素-γ（IFN-γ）也可通过YB-1负调控胶原基因表达。同时，研究发现有多种肿瘤高表达YB-1。在肝细胞癌中，YB-1与血管侵袭、肿瘤转移、疾病预后等相关，又因其特异性强，有望作为肿瘤检测的指标。     

蕲艾提取液药物血清对大鼠肝星状细胞cyclin D1蛋白表达的影响

目的：研究蕲艾提取液药物血清对大鼠肝星状细胞（HSC）细胞周期调控蛋白cyclin D1表达的影响。方法：传代培养的HSC-T6与蕲艾提取液药物血清共同培养24小时后,采用逆转录聚合酶链反应（RT-PCR）和免疫印迹（Western blot）分别检测细胞周期蛋白cyclin D1 mRNA及其蛋白表达。结果：不同浓度（5%、10%、20%）蕲艾提取液药物血清与空白对照组及血清对照各组比较,可明显抑制cyclin D1 mRNA及其蛋白表达（P〈0.01）。结论：蕲艾提取液药物血清通过抑制HSC cyclin D1 mRNA及其蛋白的表达,发挥对HSC细胞周期的调控,这可能是该药抗纤维化的机制之一。     

细胞周期素D1对HBV转录和复制的影响

目的 探究细胞周期素D1(cyclin D1,基因名CCND1)对HBV复制的影响及其机制。方法 利用GSE84044数据集，采用Spearman秩相关分析HBV相关肝纤维化患者肝组织基因表达水平与血清HBV DNA载量之间的相关性。在HBV细胞复制模型中瞬时表达cyclin D1及cyclin D1持续激活突变体(T286A)蛋白，使用时间分辨免疫荧光及实时荧光定量PCR实验分别检测细胞培养上清液中的HBsAg、HBeAg及HBV DNA水平,Western blot检测细胞内HBV core蛋白，反转录-实时荧光定量PCR法检测细胞内HBV RNA,双荧光素酶报告基因实验检测cyclin D1对HBV基本核心启动子(BCP)活性的影响。利用GSE83148数据集，分析CCND1与HBV相关调控因子表达的相关性。正态分布的计量资料两组间比较采用独立样本t检验；非正态分布的计量资料两组间比较采用Mann-Whitney U检验。结果 在GSE84044数据中,HBV相关肝纤维化患者的肝组织中有7个细胞周期调控基因与HBV DNA载量呈显著负相关(r值均<-0.3,P值均<0...     

张力蛋白同源第10染色体丢失的磷酸酶基因在胰腺癌中的表达及其与P27蛋白的关系

近年来新发现的张力蛋白同源第10染色体丢失的磷酸酶基因（PTEN）是第一个具有脂质磷酸酶活性的抑癌基因，其表达产物负性调控细胞周期及多种信号途径，抑制细胞粘附迁移，诱导细胞分化及凋亡等多种生理活动。P27是多功能细胞周期蛋白依赖性激酶抑制因子，负性调控细胞周期，是已知重要抑癌基因之一。我们应用免疫组化法研究82例胰腺癌患者肿瘤组织中PTEN及P27蛋白表达水平及相关性，分析其与胰腺癌进展及在临床评估中的意义。     

山茱萸多糖对衰老HDF细胞cyclinD1、CDK4表达的影响

目的探讨山茱萸多糖对抗人胚肺成纤维二倍体（HDF）细胞衰老的作用及其可能的细胞周期调控机制。方法体外培养HDF细／胞，实验组从40代开始加山茱萸多糖含药血清。观察细胞形态；MTr法检测细胞活力；RT—PCR法检测细胞周期蛋白（cyclin）D1、细胞周期蛋白依赖激酶（CDK）4的mRNA表达。结果衰老组细胞活力下降，cyclinD1 mRNA表达升高，CDK4mRNA表达下降；山茱萸多糖可提高细胞活力，降低cy—dinD1表达，提高CDK4表达量。结论山茱萸多糖可能通过改变细胞周期调控因子的表达而发挥其抗HDF细胞衰老作用。     

细胞周期素A与白血病

细胞周期的调控是极其复杂的,现已知在细胞周期中存在着许多检测点,这些检测点受控于细胞周期素(cyclins)、细胞周期素依赖性激酶(cyclin dependent kinase,CDK)、细胞周期素依赖性激酶抑制剂(cyclin dependent kinase inhibitor,CDI)、某些癌基因及抑癌基因的表达,其中cyclins是正性调节因子,必须与相应的CDK结合形成cyclins-CDK复合物,并经磷酸化/脱磷酸化修饰后方具有生物活性,促进与细胞周期有关的蛋白基因表达,从而对DNA合成、有丝分裂活动等进行调控.     

E1A基因对人肺腺癌细胞增殖和细胞周期的影响

目的 探讨E1A基因对人肺腺癌细胞增殖的抑制作用与细胞周期的关系及作用机制。方法 利用细胞增殖曲线和裸小鼠体内致瘤性实验研究E1A基因对人肺腺癌细胞增殖的影响,采用流式细胞术分析人肺腺癌细胞周期,以蛋白印迹方法分析P16、P21、P53和cyclin B1水平变化。结果 转染E1A基因后,人肺腺癌细胞（Anip973-E1A）生长缓慢,体内致瘤性降低。Anip973-E1A细胞周期出现明显的S期抑制和G2/M阻滞,周期调控蛋白P16、P21、P53水平无明显变化,但cyclin B1表达明显下降。结论 E1A基因能显著抑制人肺腺癌细胞的体内外增殖,降低周期蛋白cyclin B1的表达,使细胞周期阻滞于G2/M,这可能与A1A基因抑制作用有关。     

Skp2与肺癌的研究进展

肿瘤的发生的病因及机制尚未完全明确，目前所知除抑癌基因的失活，原癌基因的异常激活，DNA转录表达失控等原因外，细胞周期调控机制紊乱也是一重要因素。S期激酶相关蛋白2（S-phase kinase—associated protein2，Skp2）是新近发现的对细胞周期调控具有重要作用的基因，参与细胞的增殖与凋亡，与肿瘤的发生发展关系密切。[第一段]     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.